Biologist PZ Myers, while something of an over-the-top culture warrior -- he makes Richard Dawkins seem tactful and restrained in comparison -- does definitely light up when he's talking science and particular his specialty, cephalopods (squids, octopus, cuttlefish, etc). He recently posted an interesting set of notes on PANDA'S THUMB on the work of fellow biologist Bryan Grieg Fry, who has been exploring the evolution of animal venom. It appears that Fry's main focus has been on the evolution of lizard and snake venoms, but he has also investigated the venoms of cephalopods -- squids, cuttlefish, octopus and the like -- which is Myers' specialty. His notes followed, heavily edited for a posting on my own BBS:

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When we examine what venomous reptiles inject into their prey, it's a set of proteins that display a nested "evolutionary" hierarchy of descent. Ancient reptiles had a small and nasty set of poisons, and to improve their effectiveness, more and more have been added to the cocktail. Some lizards produce venomous proteins, while the really dangerous snakes produce those same proteins, plus a large number of others. A toxin like "Cysteine RIch Secretory Protein (CRISP)" is common to all, but only the most deadly add "phosopholipase A2 (PLA2)" -- an enzyme that breaks down cell membranes -- to the mix.

Fry has also investigated toxins in cephalopods. Fry examined the products of the venom glands of octopus, squid, and cuttlefish, and found a range of proteins -- some unique, others familiar:

CAP (a CRISP protein)

PLA2

chitinase (chitin digestive enzyme)

peptidase S1 (protein digestive enzyme)

There are several interesting lessons in that list. First, evolution doesn't just invent something entirely new on the spot to fill a function. What we find instead is that existing proteins are recycled for the new job. This is how evolution generally operates, taking what already exists and adapting it to a new function. PLA2, for example, is a perfectly harmless and extremely useful non-venomous protein in many organisms. We humans use to control the inflammation response to infection and injury , in moderation, it's a good thing. What venomous animals can do, however, is inject an overdose of this regulator to send a victim's repair and recovery systems berserk, producing swelling that can incapacitate a tissue.

Similarly, a peptidase is a useful enzyme for breaking down proteins in the digestive system "¦ but a poisonous snake or cephalopod biting your hand can squirt it into the tissues to digest your muscles and connective tissue. Some effective venoms are simply common helpful proteins being used in an unhelpful fashion -- or at least unhelpful to the victim.

Second, cephalopods and vertebrates like snakes have independently converged in using some of the same venoms. Partly this is due to the fact that the proteins were commonly available , all animals have phospholipases, which are important regulator proteins, so they are part of the common toolbox. It's also part of an inflammation pathway that can be exploited by venomous predators, in the same way that we have shared proteins used in the operation of the nervous system that can be targeted by neurotoxins.

Different animals will independently make use of these proteins as toxins, but the range of candidate proteins for toxins is common because of shared ancestry. Some of these candidates end up being more suitable for use as toxins than others. We normally don't use anything in the kitchen drawer as a weapon, but if we have to improvise the butcher knife ends up being selected far more often than the eggbeater. The CRISP proteins -- the cysteine-rich secretory proteins -- and proteins that resemble them end up being strongly preferred as toxins. The end result is that entirely different lineages of animals end up independently producing venom drawn from the same small subset of proteins.

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The posting included an evolutionary tree of the "Lepidosaurs" -- the snakes, lizards, and the iguana-like tuataras. I had to puzzle over it a bit because I only recognized a handful of the groups. What was striking was that the group not only includes snakes, but also two -- not one but two -- entirely separate groups of legless lizards, the "amphisaenids" and the very obscure "dibamids". The legless configuration just gets repeatedly invented by the lizard family.

We got to chatting about this item on my BBS and the well-known tale of the coevolution of toxic newts and garter snakes came up. Myers had a posting on PT last June on that topic, cited here, again heavily edited down:

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We've heard the arguments about the relative importance of mutations in "cis" regulatory regions versus coding sequences in evolution before , that is, the idea that major transitions in evolution were accomplished more by changes in the timing and pattern of gene expression than by significant changes in the genes themselves.

We developmental biologists tend to side with the "cis-sies", because timing and pattern are what we're most interested in. But I have to admit that there are plenty of accounts of functional adaptation in populations that are well-founded in molecular evidence -- though partly that may be an artifact of the functionalists having better tools for the moment. However, I've just received a paper per that describes a pattern of functional change in an important molecule , there is absolutely no development in it, though it is a classic example of an evolutionary arms race, though.

When I was a grad student at the University of Oregon ["Ducks" of the "People's Republic Of Eugene" -- rivals to my alma mater, Oregon State U AKA "Beavers" in Corvallis] we'd make field trips into the region's Cascade mountain range, sometimes going to a remote lake where we'd harvest rough-skinned newts, Taricha granulosa. They oozed a neurotoxin named "tetrodoxin (TTX)". If they moved into a lake, fish and frogs soon disappeared.

TTX is the same nasty substance that the "fugu", the pufferfish, contains; it blocks the sodium channels of nerve cells. Fugu is a sushi delicacy because at low concentrations it causes a tingly sensation. Overdoses can cause paralysis and death -- preparing fugu is not a task for amateurs, and clearly part of the mystique of eating it is the daring involved.

TTX is the newt's only defense. Most predators have learned to avoid them, but in the Cascades garter snakes have been adapting to the newt meal. Populations of garter snakes, T. sirtalis, in California, Oregon, and Idaho are showing different degrees of resistance to TTX, and these differences are being traced right down to specific changes in the amino acid sequence of the snake sodium channel. It's happening repeatedly, too, with different populations independently acquiring slightly different variations that confer differing degrees of resistance.

We know a lot about the structure and biophysics of the sodium channel , it's one of those universal proteins we find all over the animal kingdom. It's a protein that loops through the membrane multiple times, forming four cylindrical domains. These cylinders pack together, leaving a space at the center that is the pore proper; there are also regions of the protein that act as gates, opening to allow sodium to flow through and generate an electrical current, or closing to block it.

We also know how TTX works. It binds especially strongly to an amino acid on the outside of the cell, blocking the channel and disabling the nerve. From an evolutionary point of view, toxins are not always so hard to deal with, and in fact animals that make TTX are necessarily resistant to it, having replaced the specific amino acid that binds TTX with a different one that TTX ignores.

Now it would be straightforward for garter snakes to simply make the same swap, but evolution doesn't work that way, the snakes have not planned out the reengineering their proteins. Instead, they have rearranged the structure of the proteins in one of the channel domains in a way that interferes with TTX bindings. What is particularly interesting is that there are several different populations that are acquiring TTX resistance, but while they are all using the game "strategy" the actual tweaks being made are different. The bottom line is that we have concrete measurements of specific molecular changes that are responses to an evolutionary arms race, and we're seeing these differences emerge in different populations of single species. This is evolution in action, and the observed appearance of new properties, traced right down to single changes in proteins.

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I got to poking around in response to the June posting, being curious about the notoriously deadly "sea cones", the group of sea snails (informally speaking) that have a lethal sting. I had got the idea that the cones picked up the toxins from eating dinoflagellate plankton, which generate a neurotoxin known as "saxitoxin" -- incidentally, another sodium channel blocker. This was wrong, the cones make their own toxins, known (duh) as "conotoxins". There's a range of them, but again they are neurotoxins, not only including sodium-channel blockers but also potassium-channel and calcium-channel blockers.

Again, we have unrelated beasties that use similar toxins due to convergence. Interestingly, TTXs are also common across different groups -- not just fugu and newts -- but it may not be due to convergence, rather to symbiosis. Pufferfish raised in controlled environments are non-toxic and the TTX may be derived from symbiotic microorganisms.

Myers must be an entertaining lecturer as long as you don't get him off on politics or religion, though I suspect he knows better than to get on his soapbox on company time. Incidentally, Bryan Grieg Fry is sort of a stereotypical Aussie nature scientist, strapping skinheaded fella who tours the world chasing after venomous snakes and the like. I figured he might show up in the Discovery Channel, but a check on YouTube came up zeroes; however, a reply posting says he comes up in this video:

Yeah, poisons are awesome, and interesting... and anything awesome and interesting in science tends to debunk creationist stupidity by definition. Watching the adaptations of venoms, and resistance to venoms, is certainly more inspiring and impressive than any creationist mythology I've ever heard.

I posted this site back on the old forum. Dr. Bryan Frye has a ton of good info, some of which I think is on the evolution of venom, on his website http://www.venomdoc.com. Dr. Frye works with the Australian Venom Research Unit out of the University of Melbourne and is one of the leading experts on venom.